Reduced sodium intake normally blunts the systemic and renal vascular response to angiotensin II (AII) and potentiates the adrenal's. This normal modulation is deranged substantially in about 50% of patients with essential hypertension: the abnormality involves the kidney, the adrenal and the peripheral vasculature in the same patient and could well be responsible for the hypertension. Our overall goal is to determine the familial aggragation of this abnormality and to relate it both to the hypertension and to derangements in erythrocyte sodium transport. We will study 40 families, each consisting of both parents and at least three children. The families will be selected from a large pool (500-800) in which one sibling has already been evaluated for the presence or absence of the abnormality in renal and adrenal function. Half of the 40 families will contain an offspring who has the abnormality, the other half will have an offspring what does not. Adrenal and renovascular responses to AII and the activity of three sodium transport systems in red cells will be evaluated in each subject on both a high (200 mEq) and low (10 mEq) sodium intake. Our working premise is that the abnormality will aggregate in families: Thus, all hypertensive family members will share the same defect, which will appear only in those families. Moreover it may be present in some family members who are normatensive, who may be "prehypertensive". Furthermore, we anticipate that the adrenal and renal abnormality also will be associated with an alteration in one or more erythrocyte cation transport systems. Thus, successful completion of this project should provide data to explain the pathogenetic mechanism via which alter sodium transport produces hypertension as well as a simple marker for this subgroup of patients with essential hypertension. It would also provide a rationale for the design of a more ambitious study to determine if the biochemical abnormality documented in normotensive family members indeed is a marker for the development of essential hypertension.